Russell K. Hales and Deborah A. Frassica
Name the 2 most common types of malignant bone tumors in the pediatric population.
The 2 most common types of malignant bone tumors in the pediatric population are osteosarcoma and Ewing sarcoma.
Osteosarcoma is associated with what other pediatric tumor?
Pts with retinoblastoma have an increased risk of osteosarcoma, both within and outside the irradiated tissue.
Describe the distribution of osteosarcoma cases as a function of population age.
Osteosarcoma has a bimodal distribution as a function of age, with cases arising during the teenage years as well as cases associated with other conditions (Paget Dz, fibrous dysplasia) that arise in an older (age >65 yrs) population.
What is the incidence of osteosarcoma in the U.S. population?
400 cases/yr of osteosarcoma are diagnosed in the U.S. population, and most occur during the teenage years. Osteosarcoma is ~2 times more common than Ewing sarcoma.
What are the most common risk factors associated with the development of osteosarcoma?
High rate of bone production and turnover (as in puberty) are associated with the development of −osteosarcoma.
Describe sex and ethnic factors associated with osteosarcoma.
Osteosarcoma is more common in boys (> girls) and in blacks (> whites).
What is another name for the shaft of the bone? End of the bone?
The diaphysis is the shaft of the bone. The epiphysis is the end of the bone, and the growth plate is located in this region. The conical area of bone between the diaphysis and epiphysis is the metaphysis.
Osteosarcoma is most likely to develop in what part of the bone?
Osteosarcoma arises most frequently in the appendicular skeleton (80% of cases) at the metaphyseal portions of the femur, tibia, and humerus.
Osteosarcoma most commonly arises in which bone?
The femur is the bone in which osteosarcoma most commonly arises.
Describe the histologic defining feature of osteosarcoma.
Production of osteoid bone is the defining feature of osteosarcoma.
Describe 2 genetic syndromes associated with osteosarcoma.
Osteosarcoma is associated with Li-Fraumeni syndrome as well as retinoblastoma.
What is the difference between conventional osteosarcoma and juxtacortical osteosarcoma?
Conventional (sometimes called classic) osteosarcoma refers to the most common (75% of all cases) variant of osteosarcoma, which typically presents within areas of rapidly proliferating skeletal bone. Juxtacortical osteosarcoma refers to a set of more rare osteosarcoma variants that arise adjacent to the outer surface of −cortical bone.
Conventional osteosarcoma is usually what grade?
Conventional osteosarcoma is usually high grade.
Describe juxtacortical osteosarcoma in terms of pathologic grade and prognosis.
Juxtacortical osteosarcoma are usually low grade and rarely metastasize. They are highly curable with surgery alone and usually are located in the popliteal fossa.
What % of osteosarcoma pts have localized Dz at Dx?
90% of pts with osteosarcoma have localized Dz at Dx.
What % of osteosarcoma pts with localized Dz will develop DMs without chemo?
90% of pts with localized Dz will develop mets without chemo. (Link M et al., Clinical pediatric oncology 1991)
What are the 2 most common presenting Sx of osteosarcoma?
Pts with osteosarcoma typically present with localized bone pain (often associated with an injury) of several mos duration and a soft tissue mass.
Define the lab and radiographic studies used in the workup and staging of osteosarcoma.
Osteosarcoma workup: basic labs (CBC, CMP) as well as alk phos, LDH, and ESR. After plain films of the affected bone are obtained, MRI of the primary site is needed. PET or bone scan may be used for systemic staging of the Dz.
Define 3 principles used in the Bx of a suspected bone tumor.
Principles used in the Bx of a suspected bone tumor:
1. Bx should be performed at the same institution where the definitive resection will take place, preferably by the same surgeon who will undertake the definitive resection.
2. Bx should be placed carefully to avoid contamination of other areas, as may happen with a hematoma formation.
3. The Bx should not increase the extent of subsequent surgery.
What 3 lab values are most likely to be elevated in osteosarcoma?
Elevated alk phos, LDR, and ESR are the most likely lab abnormalities associated with osteosarcoma.
What radiographic features distinguish osteosarcoma from Ewing sarcoma?
Osteosarcoma is usually sclerotic, involves the metaphysis, and has periosteal new bone formation (sunburst pattern), whereas Ewing sarcoma is usually lytic, located in the diaphysis, and displays an onion skin effect. (Lee B et al., Handbook of radiation oncology 2007)
What is the most common site of mets from osteosarcoma?
The lung is the most common site of osteosarcoma mets.
What are the AJCC 7th edition (2009) TNM stage categories for bone tumors?
1. T1: ≤8 cm
2. T2: >8 cm
3. T3: discontinuous tumors in primary bone site
4. N0: no regional LN mets
5. N1: regional LN mets
6. M0: no DMs
7. M1a: DMs to lung
8. M1b: DMs to nonpulmonary sites
What is the AJCC stage grouping for bone tumors?
1. Stage Ia: T1N0, low grade
2. Stage Ib: T2-3N0, low grade
3. Stage IIa: T1N0, high grade
4. Stage IIb: T2N0, high grade
5. Stage III: T3N0, high grade
6. Stage IVa: M1a
7. Stage IVb: N1 or M1b
Define the Musculoskeletal Tumor Society (MSTS) staging system for bone sarcomas.
The MSTS staging system for bone sarcomas is as follows: stage I (low grade) vs. stage II (high grade), with A vs. B for anatomic extent (A, intracompartment vs. B, extracompartment). DMs are classified as stage III. Compartmental status is defined by whether the tumor extends though the cortex of the involved bone.
What is the standard Tx paradigm for osteosarcoma?
Osteosarcoma standard Tx paradigm: preop chemo → surgical resection → adj chemo.
Define 3 roles for RT in the management of osteosarcoma.
RT is useful in the management of osteosarcoma for pts with close or positive surgical margins that cannot be improved, for surgically inoperable lesions, or for palliation of painful primary tumors in pts with metastatic Dz.
What data supports the use of multiagent chemo in the management of osteosarcoma?
Multiple randomized studies have established the role of adj and neoadj chemo in osteosarcoma management. Link et al. was 1 of the 1st studies that compared multiagent chemo to no adj management in 36 pts who underwent definitive surgery. At 2 yrs, the RFS was 17% in the control group and 66% in the Tx group. (NEJM 1986)
What pathologic feature at the time of surgery is associated with chemo response and consequent improvement in outcomes with osteosarcoma?
After neoadj therapy with methotrexate/cisplatin/Adr/ifosfamide, tumor necrosis of >90% is associated with favorable outcomes. (Glasser D et al., Cancer 1991)
What is the preferred dose of RT for management of an unresectable osteosarcoma or 1 with an R2 resection (definitive paradigm)?
The preferred dose of RT in pts with gross Dz in osteosarcoma is >55 Gy. In 1 retrospective review, pts receiving doses of >55 Gy had improved LC. (DeLaney TF et al., IJROBP 2005)
What radioisotope is currently being investigated for use in the management of osteosarcoma?
Samarium-153 is currently being investigated for use in the management of osteosarcoma.
What is the 5-yr survival rate for nonmetastatic and metastatic osteosarcoma treated with chemo and surgery?
5-yr survival for nonmetastatic osteosarcoma treated with chemo and surgery is 60%–70%; for metastatic osteosarcoma, survival is ~20%.